Synthesis and in vivo evaluation of 3-[C-11]methyl-(3-methoxy-naphthalen)-2-yl-(1-benzyl-piperidin)-4-yl-acetate (SB-235753), as a putative dopamine D-4 receptors antagonist for PET

(3-Methoxy-naphthalen)-2-yl- (1-benzyl-piperidin) 4-yl-acetate (SB-235753) was labelled with C-11 (t(1/2) = 20.4 min) as a putative radioligand for th e non-invasive assessment of Dopamine D-4 receptors in vivo with positron e mission tomography (PET). The precursor for the radiosynthesis 3-hydroxynaphthyl-2-[(N-benzyl)piperid yl]-acetate hydrochloride was prepared by a four-step synthesis starting fr om ethyl-4-pyridyl acetate. The radiolabelling consisted of methylation wit h [C-11]methyltriflate in dimethylformamide in the presence of potassium hy droxide. [C-11]SB-235753, was synthesised in 30 min with a radiochemical yi eld of 10 +/- 5% (EOS, non-decay corrected) with 99% radiochemical purity a nd specific radioactivity of 10 +/- 3 Ci/mu mol. Biodistribution studies in rats with [C-11]SB-235753 showed the uniform dis tribution of the tracer within different areas of the murine brain. At 30 m in after injection 99% of the radioligand in plasma and 100% in cerebellum was metabolised. These findings-suggest that [C-11]SB-235753 can not be a s uitable tracer for dopamine D-4 receptor studies with PET.